On June 24, 2022, lisocabtagene maraleucel was approved for adults with large B-cell lymphoma (LBCL) who have (1) refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; or (2) refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age; or (3) relapsed or refractory disease after two or more lines of systemic therapy.1
Lisocabtagene maraleucel is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Breyanzi REMS.
Supporting Efficacy Data
Approval was supported by findingsfrom the TRANSFORM trial (ClinicalTrials.gov identifier NCT03575351), in which 184 transplant-eligible patients who have primary refractory LBCL or relapse within 12 months of achieving a complete response to first-line therapy were randomly assigned to a single infusion of lisocabtagene maraleucel following lymphodepleting chemotherapy (n = 92) or second-line standard therapy consisting of three cycles of chemoimmunotherapy followed by high-dose therapy and autologous HSCT in those with a complete or partial response (n = 92). Median event-free survival was 10.1 months (95% confidence interval [CI] = 6.1 months to not reached) with lisocabtagene maraleucel vs 2.3 months (95% CI = 2.2–4.3 months) with standard therapy (hazard ratio = 0.34, 95% CI = 0.22–0.52, P < .0001).
Approval was also supported by the PILOT study (NCT03483103), in which 74 transplant-ineligible patients underwent leukapheresis. Of these patients, 61 (82%) received lisocabtagene maraleucel, with a complete response in 33 (54%, 95% CI = 41%–67%); a median duration of response was not reached (95% CI = 11.2 months to not reached).
How It Is Used
The recommended dose of lisocabtagene maraleucel for second-line therapy is 90 to 110 × 106 chimeric antigen receptor–positive T cells with a 1:1 ratio of CD4 and CD8 components.
Prescribing information provides detailed instructions on management and treatment of cytokine-release syndrome and neurologic toxicities.
Among 89 patients who received lisocabtagene maraleucel in the TRANSFORM study, the most common adverse events of any grade were fever (55%), cytokine-release syndrome (49%; 1.1% grade ≥ 3), musculoskeletal pain (36%), and headache (34%). Any-grade neurologic toxicities occurred in 27% of patients (grade 3 in 7%). Serious adverse events occurred in 38% of patients, most commonly (> 2%) cytokine-release syndrome, sepsis, fever, febrile neutropenia, headache, aphasia, COVID-19 infection, and pulmonary embolism.
Among 61 patients receiving lisocabtagene maraleucel in the PILOT study, the most common adverse events of any grade were fatigue (44%), cytokine-release syndrome (39%, 1.6% grade ≥ 3), fever (38%), nausea (25%), and encephalopathy (23%). Serious adverse events occurred in 33%, most commonly (> 2%) cytokine-release syndrome, confusional state, gastrointestinal hemorrhage, muscular weakness, musculoskeletal pain, pulmonary embolism, and sepsis.
Lisocabtagene maraleucel has boxed warnings for cytokine-release syndrome and neurologic toxicities. The agent has warnings/precautions for hypersensitivity reactions, serious infections, prolonged cytopenias, hypogammaglobulinemia, secondary malignancies, and effects on the ability to drive and use machines.
1. Breyanzi (lisocabtagene maraleucel) suspension for intravenous infusion prescribing information, June 2022, Juno Therapeutics. Available at https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/breyanzi-lisocabtagene-maraleucel. Accessed August 3, 2022.